tbuckley/cabot-search huggingface dataset:
Clinical and Genomic Differences Between Advanced Molecular Imaging-detected and Conventional Imaging-detected Metachronous Oligometastatic Castration-sensitive Prostate Cancer
Authors: Philip Sutera, Yang Song, Kim Van der Eecken, Amol C. Shetty, Keara English, Theresa Hodges, Jinhee Chang, Valérie Fonteyne, Zaker Rana, Lei Ren, Adrianna A. Mendes, Nicolaas Lumen, Louke Delrue, Sofie Verbeke, Kathia De Man, Daniel Y. Song, Kenneth Pienta, Felix Y. Feng, Steven Joniau, Tamara Lotan, Barton Lane, Ana Kiess, Steven Rowe, Martin Pomper, Theodore DeWeese, Matthew Deek, Christopher Sweeney, Piet Ost, Phuoc T. Tran
Journal: European Urology (2023)

In metastatic castration-sensitive prostate cancer (mCSPC), disease volume plays an integral role in guiding treatment recommendations, including selection of docetaxel therapy, metastasis-directed therapy, and radiation to the prostate. Although there are multiple definitions of disease volume, they have commonly been studied in the context of metastases detected via conventional imaging (CIM). One such numeric definition of disease volume, termed oligometastasis, is heavily dependent on the sensitivity of the imaging modality. We performed an international multi-institutional retrospective review of men with metachronous oligometastatic CSPC (omCSPC), detected via either advanced molecular imaging alone (AMIM) or CIM. Patients were compared with respect to clinical and genomic features using the Mann-Whitney U test, Pearson's χ2 test, and Kaplan-Meier overall survival (OS) analyses with a log-rank test. A total of 295 patients were included for analysis. Patients with CIM-omCSPC had significantly higher Gleason grade group (p = 0.032), higher prostate-specific antigen at omCSPC diagnosis (8.0 vs 1.7 ng/ml; p < 0.001), more frequent pathogenic TP53 mutations (28% vs 17%; p = 0.030), and worse 10-yr OS (85% vs 100%; p < 0.001). This is the first report of clinical and biological differences between AMIM-detected and CIM-detected omCSPC. Our findings are particularly important for ongoing and planned clinical trials in omCSPC. Metastatic prostate cancer with just a few metastases only detected via newer scanning methods (called molecular imaging) is associated with fewer high-risk DNA mutations and better survival in comparison to metastatic cancer detected via conventional scan methods.
Di-valent siRNA-mediated silencing of MSH3 blocks somatic repeat expansion in mouse models of Huntington’s disease
Authors: Daniel O'Reilly, Jillian Belgrad, Chantal Ferguson, Ashley Summers, Ellen Sapp, Cassandra McHugh, Ella Mathews, Adel Boudi, Julianna Buchwald, Socheata Ly, Dimas Moreno, Raymond Furgal, Eric Luu, Zachary Kennedy, Vignesh Hariharan, Kathryn Monopoli, X. William Yang, Jeffery Carroll, Marian DiFiglia, Neil Aronin, Anastasia Khvorova
Journal: Molecular Therapy (2023)

Huntington's disease (HD) is a severe neurodegenerative disorder caused by the expansion of the CAG trinucleotide repeat tract in the huntingtin gene. Inheritance of expanded CAG repeats is needed for HD manifestation, but further somatic expansion of the repeat tract in non-dividing cells, particularly striatal neurons, hastens disease onset. Called somatic repeat expansion, this process is mediated by the mismatch repair (MMR) pathway. Among MMR components identified as modifiers of HD onset, MutS homolog 3 (MSH3) has emerged as a potentially safe and effective target for therapeutic intervention. Here, we identify a fully chemically modified short interfering RNA (siRNA) that robustly silences Msh3 in vitro and in vivo. When synthesized in a di-valent scaffold, siRNA-mediated silencing of Msh3 effectively blocked CAG-repeat expansion in the striatum of two HD mouse models without affecting tumor-associated microsatellite instability or mRNA expression of other MMR genes. Our findings establish a promising treatment approach for patients with HD and other repeat expansion diseases.
Pathogenesis and Management of Lipoprotein Disorders
Authors: Jeffrey S. Flier, Lisa H. Underhill, Ernst J. Schaefer, Robert I. Levy
Journal: New England Journal of Medicine (1985)

Lipoprotein particles transport cholesterol and triglycerides in the bloodstream. Abnormalities of plasma lipoproteins can result in a predisposition to premature coronary artery disease, pancreatitis, or neurologic disease. Recent advances in our understanding of plasma lipoprotein disorders have contributed to better diagnosis and treatment of these diseases and have provided important insights into normal lipoprotein metabolism. Our purpose is to provide a concise overview of the diagnosis, pathogenesis, and management of lipoprotein disorders.Plasma lipoproteins are generally spherical particles with a surface that consists largely of phospholipid, free cholesterol, and protein, and a core that contains mostly triglyceride and cholesterol ester. . . .
Abdominal pain in a young man revealing an infected perigastric cystic lymphangioma
Authors: Pierre Mayer, Emanuele Felli, Patrick Pessaux, Jérôme Huppertz, François Habersetzer, Lucile Héroin, Guillaume Philouze
Journal: Endoscopy (2023)

Abdominal cystic lymphangiomas are a rare pathology of childhood. They are lymphatic malformations that develop in the retroperitoneum or mesenteric space [1] [2]. They are most often asymptomatic and are revealed during an acute complication. When they are symptomatic, surgical resection is the rule [3].
Chronic ischemic ileitis after ileocecal resection and ileocolic anastomosis
Authors: Sebastian Vuola, Lucile Héroin, François Habersetzer, Guillaume Philouze, Pierre Mayer
Journal: Endoscopy (2023)

The management of precancerous colonic lesions has radically changed with the progress in endoscopy, especially therapeutic endoscopy. Large or suspected polyps were formerly managed surgically. Endoscopic submucosal dissection has completely changed the management of this kind of lesion, exposing patients to fewer postoperative complications.
Three different strategies to overcome dilation failures of the bougie cap for upper gastrointestinal refractory strictures
Authors: Marie Laugié, Jérôme Rivory, Alexandru Lupu, Florian Rostain, Pierre Lafeuille, Clara Yzet, Mathieu Pioche
Journal: Endoscopy (2023)

Benign strictures of the upper gastrointestinal tract usually require endoscopic dilation either with balloons or bougies ([Fig. 1]) as the first-line treatment. Both techniques are equivalent in terms of efficacy and safety [1], but the use of bougies has a lesser environmental impact [2]. Compared to the reusable bougies, the BougieCap (Ovesco, Tübingen, Germany) allows for visual control during dilation [3] and has proven its effectiveness and safety in patients with eosinophilic esophagitis [4] with a low weight of disposable waste.
Recruitment of gastroenterology trainees with the help of a new training model?
Authors: Hiroki Kato, Makoto Kobayashi, Motoyoshi Yano
Journal: Endoscopy (2023)

Recruitment of trainees is necessary to provide the number of gastroenterologists needed. Compared to other branches of internal medicine, gastroenterology involves many procedures, and it is thought that a sense of joy in performing procedures is a main reason why young doctors become gastroenterologists.
A successful case of endoscopic submucosal dissection using the water pressure method for hypopharyngeal carcinoma with severe fibrosis
Authors: Kurato Miyazaki, Motohiko Kato, Yusaku Takatori, Takanori Kanai, Naohisa Yahagi
Journal: Endoscopy (2023)

Endoscopic submucosal dissection (ESD) is a local treatment method for pharyngeal carcinoma that can preserve organs and maintain patients' quality of life. However, it is challenging because of the narrow and three-dimensional structure, which makes it difficult to use a traction method like with other organs. We have previously reported the usefulness of the water pressure method (WPM) in other organs [1] [2] [3] [4] [5]. In addition to the magnified effect obtained by underwater ESD, WPM makes it easier to get under the mucosal flap and identify the submucosal edge to be dissected by using the water stream. Here, we report a successful ESD using WPM for hypopharyngeal carcinoma ([Video 1]).
Waiting for the Ambulance
Authors: Maryella Desak Sirmon
Journal: Annals of Internal Medicine (2023)

Ad LibitumMay 2023Waiting for the AmbulanceMaryella Desak Sirmon, MDMaryella Desak Sirmon, MDUniversity of South Alabama Mobile, AlabamaSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M22-3067 Audio Reading - “Waiting for the Ambulance” Audio. Michael A. Lacombe, MD, Annals Associate Editor, reads “Waiting for the Ambulance” by Maryella Desak Sirmon, MD Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Will silence shatterinto razor shardswhen it's dropped,like the Roseville Water Lily vaseslipping from your handsas you fell?Will silence cringebereft and arid untilit absorbs my tear-sodden cries,like the blue moth-scarred carpetsoaks in spreading wateralong its frayed edge?Will silence kneelwith me beside you,hold you while we wait,like truth and beauty—lips muted, disappearinginto the moss of time? Author, Article, and Disclosure InformationAuthors: Maryella Desak Sirmon, MDAffiliations: University of South Alabama Mobile, AlabamaCorresponding Author: Maryella Desak Sirmon, MD; e-mail, mdsirmon@aol.com. PreviousarticleNextarticle Advertisement Audio Reading - “Waiting for the Ambulance” Audio. Michael A. Lacombe, MD, Annals Associate Editor, reads “Waiting for the Ambulance” by Maryella Desak Sirmon, MD Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetailsSee AlsoFifty in the Sock Drawer Maryella Desak Sirmon Star Stuff Maryella Desak Sirmon Star Stuff Maryella Desak Sirmon Metrics May 2023Volume 176, Issue 5Page: 730 ePublished: 16 May 2023 Issue Published: May 2023 Copyright & PermissionsCopyright © 2023 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
A living ex vivo platform for functional, personalized brain cancer diagnosis
Authors: Breanna Mann, Xiaopei Zhang, Noah Bell, Adebimpe Adefolaju, Morrent Thang, Rajaneekar Dasari, Krishna Kanchi, Alain Valdivia, Yang Yang, Andrew Buckley, Vivien Lettry, Carolyn Quinsey, Yasmeen Rauf, David Kram, Noah Cassidy, Cyrus Vaziri, David L. Corcoran, Stephen Rego, Yuchao Jiang, Lee M. Graves, Denise Dunn, Scott Floyd, Albert Baldwin, Shawn Hingtgen, Andrew B. Satterlee
Journal: Cell Reports Medicine (2023)

Functional precision medicine platforms are emerging as promising strategies to improve pre-clinical drug testing and guide clinical decisions. We have developed an organotypic brain slice culture (OBSC)-based platform and multi-parametric algorithm that enable rapid engraftment, treatment, and analysis of uncultured patient brain tumor tissue and patient-derived cell lines. The platform has supported engraftment of every patient tumor tested to this point: high- and low-grade adult and pediatric tumor tissue rapidly establishes on OBSCs among endogenous astrocytes and microglia while maintaining the tumor's original DNA profile. Our algorithm calculates dose-response relationships of both tumor kill and OBSC toxicity, generating summarized drug sensitivity scores on the basis of therapeutic window and allowing us to normalize response profiles across a panel of U.S. Food and Drug Administration (FDA)-approved and exploratory agents. Summarized patient tumor scores after OBSC treatment show positive associations to clinical outcomes, suggesting that the OBSC platform can provide rapid, accurate, functional testing to ultimately guide patient care.
Improving COVID-19 Disease Severity Surveillance Measures: Statewide Implementation Experience
Authors: Shira Doron, Paul A. Monach, Catherine M. Brown, Westyn Branch-Elliman
Journal: Annals of Internal Medicine (2023)

Measurement of the burden of COVID-19 on U.S. hospitals has been an important element of the public health response to the pandemic. However, because of variation in testing density and policies, the metric is not standardized across facilities. Two types of burdens exist, one related to the infection control measures that patients who test positive for SARS-CoV-2 require and one from the care of severely ill patients receiving treatment of COVID-19. With rising population immunity from vaccination and infection, as well as the availability of therapeutics, severity of illness has declined. Prior research showed that dexamethasone administration was highly correlated with other disease severity metrics and sensitive to the changing epidemiology associated with the emergence of immune-evasive variants.On 10 January 2022, the Massachusetts Department of Public Health began requiring hospitals to expand surveillance to include reports of both the total number of "COVID-19 hospitalizations" daily and the number of inpatients who received dexamethasone at any point during their hospital stay. All 68 acute care hospitals in Massachusetts submitted COVID-19 hospitalization and dexamethasone data daily to the Massachusetts Department of Public Health over a 1-year period. A total of 44 196 COVID-19 hospitalizations were recorded during 10 January 2022 to 9 January 2023, of which 34% were associated with dexamethasone administration. The proportion of patients hospitalized with COVID-19 who had received dexamethasone was 49.6% during the first month of surveillance and decreased to a monthly average of approximately 33% by April 2022, where it has remained since (range, 28.7% to 33%).Adding a single data element to mandated reporting to estimate the frequency of severe COVID-19 in hospitalized patients was feasible and provided actionable information for health authorities and policy makers. Updates to surveillance methods are necessary to match data collection with public health response needs.
Engineer a double team of short-lived and glucose-sensing bacteria for cancer eradication
Authors: Ye Jin, Li Fu
Journal: Cell Reports Medicine (2023)

Rationally designed and engineered bacteria represent an emerging unique approach for cancer treatment. Here, we engineer a short-lived bacterium, mp105, that is effective against diverse cancer types and safe for intravenous administration. We reveal that mp105 combats cancer by direct oncolysis, depletion of tumor-associated macrophages, and elicitation of CD4+ T cell immunity. We further engineer a glucose-sensing bacterium named m6001 that selectively colonizes solid tumors. When intratumorally injected, m6001 clears tumors more efficiently than mp105 due to its post-delivery replication in tumors and potent oncolytic capacity. Finally, we combine intravenous injection of mp105 and intratumoral injection of m6001, forming a double team against cancer. The double team enhances cancer therapy compared with single treatment for subjects carrying both intratumorally injectable and uninjectable tumors. The two anticancer bacteria and their combination are applicable to different scenarios, turning bacterial therapy for cancer into a feasible solution.
Heart Failure
Authors: Joseph Zarconi
Journal: Annals of Internal Medicine (2023)

On Being a DoctorMay 2023Heart FailureJoseph Zarconi, MDJoseph Zarconi, MDNortheast Ohio Medical University, Rootstown, OhioAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M23-0349 Audio Reading - "Heart Failure" Audio. Michael A. Lacombe, MD, Annals Associate Editor, reads "Heart Failure" by Joseph Zarconi, MD Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail The disease had sharpened my senses—not destroyed—not dulled them.—Edgar Allan Poe, "The Tell-Tale Heart"I hated her. In some ways, I hated myself for hating her. The oath I had taken prohibited it but gave me no guidance about how to manage those feelings or even any indication that they would come. The fatigue, workload, demands, pressure, isolation, suppressed emotions, and all else that is internship made the guilt fleeting enough to seem less troubling and perhaps even justifiable. In time, I became certain. I hated her. She initiated every conversation with, "You ain't shit." My on-call experiences had been ... Author, Article, and Disclosure InformationAuthors: Joseph Zarconi, MDAffiliations: Northeast Ohio Medical University, Rootstown, OhioCorresponding Author: Joseph Zarconi, MD; e-mail, jzarconi@neomed.edu. PreviousarticleNextarticle Advertisement Audio Reading - "Heart Failure" Audio. Michael A. Lacombe, MD, Annals Associate Editor, reads "Heart Failure" by Joseph Zarconi, MD Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics May 2023Volume 176, Issue 5Page: 728-729 ePublished: 16 May 2023 Issue Published: May 2023 Copyright & PermissionsCopyright © 2023 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Annals Consult Guys - Noncardiac Surgery Following COVID-19: A Coast-to-Coast Update
Authors: Howard H. Weitz, Geno J. Merli, Avital Y. O’Glasser
Journal: Annals of Internal Medicine (2023)

Web ExclusivesMay 2023Annals Consult Guys - Noncardiac Surgery Following COVID-19: A Coast-to-Coast UpdateFREEHoward H. Weitz, MD, Geno J. Merli, MD, and Avital Y. O’Glasser, MDHoward H. Weitz, MDThomas Jefferson University, Philadelphia, Pennsylvania (H.H.W., G.J.M.)Search for more papers by this author, Geno J. Merli, MDThomas Jefferson University, Philadelphia, Pennsylvania (H.H.W., G.J.M.)Search for more papers by this author, and Avital Y. O’Glasser, MDOregon Health & Science University, Portland, Oregon (A.Y.O.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W22-0018 CME/MOC SectionsSupplemental MaterialAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail The Annals Consult Guys discuss the appropriate timing of elective surgery in patients following COVID-19. Have recommendations changed since early in the pandemic?For more videos from and information on Annals Consult Guys, visit go.annals.org/ConsultGuys. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAuthors: Howard H. Weitz, MD; Geno J. Merli, MD; Avital Y. O’Glasser, MDAffiliations: Thomas Jefferson University, Philadelphia, Pennsylvania (H.H.W., G.J.M.)Oregon Health & Science University, Portland, Oregon (A.Y.O.)Disclosures: Drs. Merli, Weitz, and O’Glasser report that they have no financial relationships or interests to disclose. All relevant financial relationships have been mitigated. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=W22-0018.Editors' Disclosures: The editors have no relevant financial relationships to disclose. Individual forms may be viewed at www.annals.org/editorsdisclosures. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics May 2023Volume 176, Issue 5 ePublished: 16 May 2023 Issue Published: May 2023 Copyright & PermissionsCopyright © 2023 by American College of Physicians. All Rights Reserved.Loading ...
Prox2 and Runx3 vagal sensory neurons regulate esophageal motility
Authors: Elijah D. Lowenstein, Pierre-Louis Ruffault, Aristotelis Misios, Kate L. Osman, Huimin Li, Rachel S. Greenberg, Rebecca Thompson, Kun Song, Stephan Dietrich, Xun Li, Nikita Vladimirov, Andrew Woehler, Jean-François Brunet, Niccolò Zampieri, Ralf Kühn, Stephen D. Liberles, Shiqi Jia, Gary R. Lewin, Nikolaus Rajewsky, Teresa E. Lever, Carmen Birchmeier
Journal: Neuron (2023)

Vagal sensory neurons monitor mechanical and chemical stimuli in the gastrointestinal tract. Major efforts are underway to assign physiological functions to the many distinct subtypes of vagal sensory neurons. Here, we use genetically guided anatomical tracing, optogenetics, and electrophysiology to identify and characterize vagal sensory neuron subtypes expressing Prox2 and Runx3 in mice. We show that three of these neuronal subtypes innervate the esophagus and stomach in regionalized patterns, where they form intraganglionic laminar endings. Electrophysiological analysis revealed that they are low-threshold mechanoreceptors but possess different adaptation properties. Lastly, genetic ablation of Prox2 and Runx3 neurons demonstrated their essential roles for esophageal peristalsis in freely behaving mice. Our work defines the identity and function of the vagal neurons that provide mechanosensory feedback from the esophagus to the brain and could lead to better understanding and treatment of esophageal motility disorders.
Synaptic oligomeric tau in Alzheimer’s disease — A potential culprit in the spread of tau pathology through the brain
Authors: Martí Colom-Cadena, Caitlin Davies, Sònia Sirisi, Ji-Eun Lee, Elizabeth M. Simzer, Makis Tzioras, Marta Querol-Vilaseca, Érika Sánchez-Aced, Ya Yin Chang, Kristjan Holt, Robert I. McGeachan, Jamie Rose, Jane Tulloch, Lewis Wilkins, Colin Smith, Teodora Andrian, Olivia Belbin, Sílvia Pujals, Mathew H. Horrocks, Alberto Lleó, Tara L. Spires-Jones
Journal: Neuron (2023)

In Alzheimer's disease, fibrillar tau pathology accumulates and spreads through the brain and synapses are lost. Evidence from mouse models indicates that tau spreads trans-synaptically from pre- to postsynapses and that oligomeric tau is synaptotoxic, but data on synaptic tau in human brain are scarce. Here we used sub-diffraction-limit microscopy to study synaptic tau accumulation in postmortem temporal and occipital cortices of human Alzheimer's and control donors. Oligomeric tau is present in pre- and postsynaptic terminals, even in areas without abundant fibrillar tau deposition. Furthermore, there is a higher proportion of oligomeric tau compared with phosphorylated or misfolded tau found at synaptic terminals. These data suggest that accumulation of oligomeric tau in synapses is an early event in pathogenesis and that tau pathology may progress through the brain via trans-synaptic spread in human disease. Thus, specifically reducing oligomeric tau at synapses may be a promising therapeutic strategy for Alzheimer's disease.
The decline of science at the FDA has become unmanageable
Authors: David B Ross
Journal: BMJ (2023)

clinical professor of medicineBefore 1962, US federal law did not require pre-marketing proof of effectiveness for drugs.But senate hearings revealing widespread false advertising of drugs-along with the thalidomide safety disaster-spurred Congress into action.From then on, approval of a New Drug Application (NDA) by the US Food and Drug Administration required proof of "substantial evidence" of effectiveness.This proof was defined as results from "adequate and well-controlled investigations, including clinical investigations," 1 with such evidence also required to advertise claims of safety and effectiveness.A National Academy of Sciences review underscored the need for these mandates, finding over 30% of pre-1962 marketed drugs to be ineffective.